1. Field of the Invention
The present invention relates to a method of fabricating an integral device of a biochip and the apparatus thereof, especially relates to a method of fabricating an integral device of a biochip integrated with micro thermo-electric elements and the apparatus thereof.
2. Description of the Prior Art
The polymerase chain reaction (PCR) was invented by Kary Mullis at 1985. The PCR is an artificial copy technique simulated and simplified from the idea of the Deoxyribonucleic Acid (DNA) replication. The PCR can exactly increase the weight of the specific interval of the DNA at very short time in the test tube and the weight of the original DNA is increased from few picograms to few micrograms even to few milligrams. Because of the increase of the signal, an easy and fast method is provided to detect the virus, breed the DNA, diagnosis the disease and identify by the legal medical expert.
The following is the description of the theory and the method of the PCR. At first, the DNA template is heated to 95 centigrade degrees. When the DNA of the double helix will be split into two strands, the step is called the denaturation. Then, the temperature of the test tube will go down to 65 centigrade degrees and the primer pair and the single strand DNA start to stick together. The step is called annealing. Finally, the temperature will increase to 75 centigrade degrees and the compound enzyme of the DNA can duplicate the single strand DNA, which is stuck with the primer pair, at the range of the suitable temperature. At the time, the gene chain, which is formed in the previous step, can be extended and this step is called extension. After the three steps described above, it is called a cycle. Those steps repeat again and again, and the product can be rapidly produced at the speed of 2N.
The introduction of the circulated steps described above, it is known that the reaction of the PCR need to do the temperature control by increasing or decreasing the temperature. Therefore, the range of the temperature control is the key point for the reaction of the PCR. It should avoid increasing the temperature too high for the normal type of the DNA, and the DNA would be damaged by the higher temperature and the probability of the error of the duplication can be increased. On the other hand, if the temperature of the cycle is too low, such as the step of the denaturation, the temperature reaction is lower than 95 centigrade degrees, the two strands DNA cannot be split into single. And the following steps cannot be completed. Therefore, the temperature control is very important for the PCR reaction.
Those PCR machine sold in the market, the management of the temperature control can use the following methods: Peltier device, resistive/water, light, electric coil/air, circulating air and so on. In the comparison of the speed of increasing the temperature, there is no big different among those methods described above. However, in the comparison of the speed of decreasing the temperature, the Peltier device can automatically decrease the temperature without using additional materials, such as water or air. Because of this, the Peltier device is become the main stream in the market.
It is the research trend to minimize the PCR reaction. The minimization solve many drawbacks, such as big volume, heavy machine, big operative power, and large value of the reactive reagent, and increase the cycle reaction time of the PCR. The conventional micro PCR reaction includes two of the following types: (1) chamber-type PCR, and (2) continuous-flow PCR. The method to increase or decrease the temperature of the micro PCR described above is using the metal wire to heat, wherein the chamber-type PCR is using the metal wire to heat the wall of the chamber and then transfer it from the chamber to the reactive fluid. By switching the temperature of the chamber high or low, the three temperature ranges can be reached by the reactive need PCR. Controversy, the continuous-flow PCR is directly heating the fluid from the bottom, and the density of the metal wire is used to achieve the three temperature ranges of the reaction. These two methods described above to decrease the temperature are using the convection air to cool down. Besides, there are a few related researches produced reactive continuous channel and chamber, and dispose a Peltier device below the reactive continuous channel and the chamber that is used to be the tool to increase or decrease the temperature. The temperature produced by the Peltier device is transferred to the adherent material from the backboard of the Peltier device and to the continuous channel and the material of the reactive room then transfer to the reactive fluid.
Most of the PCR device used to increase or decrease the temperature is the Peltier device. For example, there are four different temperature ranges can be used to heat up or down by the Peltier device to have different temperature reaction. When the heated range is achieved the temperature of the need, the rotated device can be used to move the reactive reagent to the temperature range of the need. Besides, in the micro PCR chip, the Peltier device can be directly stuck in the back of the PCR chip to be the cooler for increasing or decreasing the temperature. In another prior art, the micro chamber-type PCR is used. And the metal wire and the air are used to decrease the temperature for the need of the chamber-type PCR. The size of the chamber-type PCR is used to adjust and control the value of the reactive reagent. The design of the double side metal membrane heater is used to control the temperature more easily. Besides, in another prior art, the micro chamber-type PCR utilizes the method of pressurizing fabrication to fabricate the chamber-type PCR, thermo-electric elements, heat dissipation fin, chamber covered into one unity. The chamber is made by slim material to reduce the value of the reagent and is using the thermoelectric element, which is stuck in the bottom of the chamber, to control the temperature.